Research Spotlight: Improving Treatment Solutions for Eosinophilic Esophagitis (EoE)

Davis A. Hartnett, MD, and Mayssan Muftah, MD, MPH, of the Division of Gastroenterology, Hepatology and Endoscopy at Brigham and Women’s Hospital, are co-lead authors of a paper published in Clinical Gastroenterology and Hepatology, “Distribution of Esophageal Eosinophilia as a Predictor of Proton Pump Inhibitor Response in Eosinophilic Esophagitis.”

Q: How would you summarize your study for a lay audience?

Eosinophilic Esophagitis (EoE) is a chronic condition characterized by inflammation in the esophagus in response to food and environmental allergens.

EoE can cause symptoms such as difficulty swallowing, chest pain, and/or regurgitation, and may lead to complications such as food impaction. In recent years, rates of EoE are on the rise, but tailoring treatment methods to each patient remains a difficult task and is often done through trial and error.

In this study, we sought to determine whether the location of eosinophils, the inflammatory cells in the esophagus that are used to diagnose the disease, could help determine which treatment may work best for each patient.

By looking at the biopsy results and treatment outcomes of 266 patients, we found that specific patterns of eosinophil distribution at diagnosis could help to identify different disease presentations and guide treatment decisions.

Q: What question were you investigating?

As allergic conditions such as asthma, eczema, and EoE become more prevalent, there exists a growing need to understand these conditions and how they respond to treatment. The definitive management of EoE is far less understood than similar conditions, as what we know about the disease has changed immensely in the last two decades.

Proton pump inhibitor (PPI) therapy, which is a medication that reduces stomach acid, is very effective for some patients with EoE, but as many as half of them do not see significant improvement with this treatment. To add to the challenge, there is currently no reliable way to clinically predict which patients may respond to PPI without a prolonged treatment trial and a follow-up endoscopy to assess response. This current approach may, therefore, delay getting the disease under control for those who are non-responders to PPI. Because EoE requires an upper endoscopy with esophagus biopsies to be diagnosed, we aimed to determine whether the data collected at the time of the initial endoscopy could also be helpful in determining treatment.

If we could assess whether a patient would be likely to respond to PPI therapy from the start, it would expedite our ability to provide effective care.

Q: What method or approach did you use?

We have developed one of the largest patient databases dedicated to EoE, which includes comprehensive information on patient demographics, comorbidities, endoscopic findings, pathology results, treatment strategies and outcomes.

We identified 266 patients within this database who had the distribution of their eosinophils throughout the esophagus assessed at diagnosis and were treated with PPI. These patients were stratified based on the distribution of eosinophils throughout the esophagus.

Our study compared patients with distal eosinophilia, meaning higher numbers of cells in the lower esophagus, and patients with either proximal eosinophilia (higher numbers of cells in the upper esophagus) or diffuse numbers of cells throughout. We compared the rates at which patients responded to PPI treatment between the two groups, while controlling for other potential confounders.

Q: What did you find?

We found that patients with eosinophil-associated inflammation isolated to the lower esophagus were more likely to respond to PPI treatment than those with inflammation throughout the esophagus or isolated to the upper esophagus.

Q: What are the implications?

Our study is one of the largest to examine the impact of eosinophil distribution (measured at the time of diagnosis) on treatment outcomes.

Currently, to determine whether a treatment is effective, patients must undergo the initial EoE diagnostic endoscopy, test out a treatment, and then undergo another endoscopy to check for a reduction in eosinophils.

With this new test, we may now be able to provide better and more targeted treatment recommendations based on the initial diagnostic endoscopy, potentially reducing medical testing and overall time to disease remission.

Our results also provide further insight into the complicated mechanism underlying EoE, as well as the many different phenotypes of this complex disease.

Q: What are the next steps?

Our study demonstrates one possible variable, the distribution of eosinophils, that may guide treatment at EoE diagnosis. Future studies may prospectively validate this finding and combine it with other clinical variables that can predict treatment response at the time of diagnosis (many of which had previously been identified by prior work of our group, such as blood eosinophil count, history of allergic conditions, etc.).

We hope to leverage this and our prior work to build prediction models to inform clinical decision making and help clinicians formulate targeted and personalized approach for treatment of EoE.

We also plan to better understand the phenotypes and pathophysiology of EoE by further exploring these clinical variables at a molecular level.

Authorship: In addition to Hartnett and Muftah, Mass General Brigham authors include Brent Hiramoto, Ryan Flanagan, Jennifer X. Cai, Wai-Kit Lo, and Walter W. Chan.

Paper cited: Hartnett, D. A., et al. “Distribution of Esophageal Eosinophilia as a Predictor of Proton Pump Inhibitor Response in Eosinophilic Esophagitis.” Clinical Gastroenterology and Hepatology. DOI: https://doi.org/10.1016/j.cgh.2025.06.032

Funding: This work was supported by grants from the National Institute of Health (T32 DK135449/DK/NIDDK NIH HHS/United States)

Disclosures: Walter Chan served on the advisory board for Sanofi Pharmaceuticals and Regeneron Pharmaceuticals. No other authors have potential conflicts of interest to disclose.